Reversible Oligonucleosome Self-Association:  Dependence on Divalent Cations and Core Histone Tail Domains

Schwarz, Patricia M.; Felthauser, Alicia; Fletcher, Terace M.; Hansen, Jeffrey C.

doi:10.1021/bi9525684

Cited by 239 publications

(328 citation statements)

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“…This is followed by further condensation into a maximally folded ϳ55 S structure whose extent of compaction is equivalent to the classical 30-nm diameter fiber (1,6,8,11). The final condensation transition involves reversible, cooperative oligomerization of individual 208-12 arrays into higher order polymeric species (1,7). Given that the low salt structures of the tailless and intact chromatin arrays assembled in these studies were nearly identical (Fig.…”

Section: Assembly and Characterization Of Intact And Tailless Nucleosmentioning

confidence: 77%

“…The condensation process involves a complex series of hierarchical folding and oligomerization transitions (4 -7). Nucleosomal arrays that lack their core histone N termini ("tail domains") are unable to either fold (5,8,9) or oligomerize (7,8,10), indicating that the tail domains are absolutely required for nucleosomal array condensation. However, the folded states of nucleosomal arrays are not intrinsically stable (4,5,6,11).…”

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confidence: 99%

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The Core Histone N Termini Function Independently of Linker Histones during Chromatin Condensation

Carruthers

Hansen

2000

Journal of Biological Chemistry

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114

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The relationships between the core histone N termini and linker histones during chromatin assembly and saltdependent chromatin condensation were investigated using defined chromatin model systems reconstituted from tandemly repeated 5 S rDNA, histone H5, and either native "intact" core histone octamers or "tailless" histone octamers lacking their N-terminal domains. Nuclease digestion and sedimentation studies indicate that H5 binding and the resulting constraint of entering and exiting nucleosomal DNA occur to the same extent in both tailless and intact chromatin arrays. However, despite possessing a normal chromatosomal structure, tailless chromatin arrays can neither condense into extensively folded structures nor cooperatively oligomerize in MgCl 2 . Tailless nucleosomal arrays lacking linker histones also are unable to either fold extensively or oligomerize, demonstrating that the core histone N termini perform the same functions during salt-dependent condensation regardless of whether linker histones are components of the array. Our results further indicate that disruption of core histone N termini function in vitro allows a linker histone-containing chromatin fiber to exist in a decondensed state under conditions that normally would promote extensive fiber condensation. These findings have key implications for both the mechanism of chromatin condensation, and the regulation of genomic function by chromatin.

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Section: Assembly and Characterization Of Intact And Tailless Nucleosmentioning

confidence: 77%

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confidence: 99%

The Core Histone N Termini Function Independently of Linker Histones during Chromatin Condensation

Carruthers

Hansen

2000

Journal of Biological Chemistry

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114

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“…With increased Mg 2ϩ concentration, nucleosomal arrays undergo reversible self-association (42) attributed to the formation of global tertiary chromatin structures (4). When ϩLHϩMg arrays are crosslinked at 4 mM MgCl 2 (where the material was completely self-associated: Fig.…”

Section: Internucleosomal Interactions Mapping By Emanicmentioning

confidence: 99%

Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions

Grigoryev

Arya

Correll

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

245

358

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The architecture of the chromatin fiber, which determines DNA accessibility for transcription and other template-directed biological processes, remains unknown. Here we investigate the internal organization of the 30-nm chromatin fiber, combining Monte Carlo simulations of nucleosome chain folding with EM-assisted nucleosome interaction capture (EMANIC). We show that at physiological concentrations of monovalent ions, linker histones lead to a tight 2-start zigzag dominated by interactions between alternate nucleosomes (i ؎ 2) and sealed by histone N-tails. Divalent ions further compact the fiber by promoting bending in some linker DNAs and hence raising sequential nucleosome interactions (i ؎ 1). Remarkably, both straight and bent linker DNA conformations are retained in the fully compact chromatin fiber as inferred from both EMANIC and modeling. This conformational variability is energetically favorable as it helps accommodate DNA crossings within the fiber axis. Our results thus show that the 2-start zigzag topology and the type of linker DNA bending that defines solenoid models may be simultaneously present in a structurally heteromorphic chromatin fiber with uniform 30 nm diameter. Our data also suggest that dynamic linker DNA bending by linker histones and divalent cations in vivo may mediate the transition between tight nucleosome packing within discrete 30-nm fibers and self-associated higher-order chromosomal forms.chromatin structure ͉ electron microscopy ͉ mesoscopic modeling ͉ Monte Carlo simulations ͉ linker histone T he DNA in eukaryotic chromatin is packed and functionally regulated by histones and nonhistone architectural proteins (1). The primary packing level is represented by an array of repeating units, the nucleosomes, where the DNA is wound around histone octamers (2). Further compaction is achieved through a hierarchy of folding levels, including the 30-nm chromatin fiber (secondary level) and more compact and self-associating tertiary and quaternary forms whose structures are unknown (3-6). Because DNA conformation in chromatin and nucleosome packing are intimately connected to DNA/protein recognition and gene regulation, there has been intense interest in understanding chromatin structure, energetics, and dynamics. Some experimental studies have suggested that nucleosomal arrays fold in a zigzag arrangement with relatively straight linkers and a 2-start nucleosome interaction pattern that brings each nucleosome in proximity to its second nearest neighbor (7-10) consistent with chromatin fibers observed in situ (11). Other evidence suggests that chromatin condensed with linker histones and divalent cations such as Mg 2ϩ can form either zigzag structures with various nucleosome topologies (12, 13) or solenoid-like arrangements. The latter class of structures has bent DNA linkers and predominant interactions between either nearest neighbor nucleosomes (14, 15) and/or between every fifth or sixth nucleosome along the chain (16,17).The picture has became more complex recently with our heighte...

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“…The solution properties of DNA, which were once interpreted in terms of the stacking interactions of bases, resemble the features of strong internucleosomal association in chromatin detected with modern force-extension technology (50) or classic electric dichroism measurements (51). Classic polymer studies of chromatin offer the same sort of insights into overall macromolecular structure as did early studies of DNA, including how the composition and number of side groups (nucleosomes as opposed to bases) influence global chain dimensions (52). Models of DNA fibers deduced from x-ray diffraction studies raised questions about structural motifs (53) along the same lines as questions raised in recent years about the spatial disposition of nucleosomes in chromatin (7,8).…”

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confidence: 87%

Contributions of Sequence to the Higher-Order Structures of DNA

Todolli

Perez

Clauvelin

et al. 2017

Biophysical Journal

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One of the critical unanswered questions in genome biophysics is how the primary sequence of DNA bases influences the global properties of very-long-chain molecules. The local sequence-dependent features of DNA found in high-resolution structures introduce irregularities in the disposition of adjacent residues that facilitate the specific binding of proteins and modulate the global folding and interactions of double helices with hundreds of basepairs. These features also determine the positions of nucleosomes on DNA and the lengths of the interspersed DNA linkers. Like the patterns of basepair association within DNA, the arrangements of nucleosomes in chromatin modulate the properties of longer polymers. The intrachromosomal loops detected in genomic studies contain hundreds of nucleosomes, and given that the simulated configurations of chromatin depend on the lengths of linker DNA, the formation of these loops may reflect sequence-dependent information encoded within the positioning of the nucleosomes. With knowledge of the positions of nucleosomes on a given genome, methods are now at hand to estimate the looping propensities of chromatin in terms of the spacing of nucleosomes and to make a direct connection between the DNA base sequence and larger-scale chromatin folding.Despite the astonishing amount of information now known about the sequential makeup and spatial organization of genomic DNA, there is much to learn about how the vast numbers of basepairs in these systems contribute to the three-dimensional architectures and workings of long, spatially constrained, double-helical molecules. New biochemical and imaging methodologies, such as proximity-based ligation and fluorescence in situ hybridization (1-3), have shed light on the large-scale organization of genomic DNA, enabling investigators to pinpoint DNA elements in close spatial proximity and follow the course of these associations during cellular processes. The resulting measurements have motivated the study of long genomes in terms of simple polymer models (4,5), which have in turn illuminated the physical nature of the contacted elements and pointed to mechanisms potentially governing genome architecture and dynamics. Although these models are appropriate for the very large scale of the experimental data, they rest on the assumption that the chemical makeup of DNA does not matter, and thus provide no link between the primary sequence of bases and the tertiary structures and interactions of genomic folds.At the other extreme of chain length, the detailed molecular structures of DNA with only tens of basepairs point to various sequence-dependent spatial and energetic codes underlying the three-dimensional organization of the double helix and its susceptibility to interactions with proteins and other molecules (6). The structural data also include more than 100 crystallographic examples of the tight, superhelical wrapping of~150 DNA basepairs (bp) around the core of the histone proteins in the nucleosome core particle, the fundamental packagi...

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Reversible Oligonucleosome Self-Association: Dependence on Divalent Cations and Core Histone Tail Domains

Cited by 239 publications

References 38 publications

The Core Histone N Termini Function Independently of Linker Histones during Chromatin Condensation

The Core Histone N Termini Function Independently of Linker Histones during Chromatin Condensation

Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions

Contributions of Sequence to the Higher-Order Structures of DNA

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